rs709209

Positions:

• chr1-6218354-A-C
• chr1-6218354-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207396.3(RNF207):​c.1718A>C​(p.Asn573Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N573S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF207 NM_207396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

Genes affected

RNF207 (HGNC:32947): (ring finger protein 207) Enables Hsp70 protein binding activity; chaperone binding activity; and transmembrane transporter binding activity. Involved in positive regulation of delayed rectifier potassium channel activity; positive regulation of gene expression; and positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03907174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF207	NM_207396.3	c.1718A>C	p.Asn573Thr	missense_variant	17/18	ENST00000377939.5	NP_997279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF207	ENST00000377939.5	c.1718A>C	p.Asn573Thr	missense_variant	17/18	5	NM_207396.3	ENSP00000367173	P1
RNF207	ENST00000483336.1	n.350A>C		non_coding_transcript_exon_variant	3/4	3
RNF207	ENST00000496676.5	n.1435A>C		non_coding_transcript_exon_variant	9/10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.6
DANN	Benign	0.31
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.018
Sift	Benign	0.66	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.073		Gain of phosphorylation at N573 (P = 0.0225);
MVP		0.048
MPC		0.17
ClinPred		0.024	T
GERP RS		-1.3
Varity_R		0.032
gMVP		0.073

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs709209; hg19: chr1-6278414;